Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease

We partitioned exhaled nitric oxide (NO) into alveolar concentration (CA) and conducting airway flux (JNO_air,max) in scleroderma (SSc) lung disease and hypothesized that CA would be elevated. Twenty patients with SSc, 15 with interstitial lung disease (SSc-ILD) alone, and 5 with pulmonary hypertension (SSc-PH) were compared with 20 control subjects. CA and JNO_air,max were derived from the slope and y intercept, respectively, of the NO output versus expiratory flow rate (Vexh) relationship obtained by measuring exhaled NO (FE_NO) at multiple Vexh values of 50-200 ml/second. There were no significant differences in FE_NO at any V̇exh between the SSc group and control subjects. JNO_air,max was reduced (0.6 ± 0.1 versus 1.2 ± 0.2 nl of NO per second; p = 0.01), whereas CA was increased (4.7 ± 0.5 versus 1.8 ± 0.2 ppb; p < 0.001) in the SSc group compared with control subjects. No differences were noted between SSc-ILD and SSc-PH. There was a negative correlation between CA and DL_CO among the patients with SSc (R = -0.66, p = 0.002). We conclude that CA is increased whereas JNO_air,max is decreased in SSc-ILD and SSc-PH. A reduced diffusing capacity of NO from the alveolar space into the blood could explain the observed increase in CA.